PI3K/HDAC Inhibitor 是一种 I 型PI3K及 I 和 II 型HDAC酶抑制剂,作用于 PI3Kα/PI3Kβ/PI3Kδ 和 HDAC1/HDAC2/HDAC3/HDAC10 ,IC50分别为 19/54/39 nM 和 1.7/5.0/1.8/2.8 nM。
产品描述
CUDC-907 is an orally bioavailable inhibitor of both phosphoinositide 3-kinase (PI3K) class I and pan-histone deacetylase (HDAC) enzymes, with potential antineoplastic activity. Upon oral administration, CUDC-907 inhibits the activity of both PI3K class I isoforms and HDAC, thereby preventing the activation of the PI3K-AKT-mTOR signal transduction pathway that is often overactivated in many cancer cell types.
体外活性
在作用于NHL和MM模型的高效性研究中, CUDC-907按最大耐受剂量处理,比单独药剂PI3K或HDAC抑制剂或两者联用效果更明显.且按最大耐受剂量处理,CUDC-907比PI3Kδ选择性抑制剂CAL-101更有效.CUDC-907对犬类具有口服生物有效性.CUDC-907在小鼠肿瘤中的半衰期较长.作用于移植瘤时,CUDC-907诱导凋亡并抑制癌细胞增殖.
体内活性
CUDC-907对一系列B细胞淋巴瘤的生长具有抑制作用,如Granta 519(IC50:7 nM),DOHH2(IC50:1 nM),RL(IC50:2 nM),Pfeiffer(IC50:4 nM),SuDHL4(IC50:3 nM),Daudi(IC50:15 nM) 和 Raji(IC50:9 nM)。CUDC-907对骨髓瘤增殖也有阻断作用,如RPMI8226(IC50:2 nM),OPM-2(IC50:1 nM)和ARH77(IC50:5 nM)。CUDC-907对多发性骨髓瘤和B细胞淋巴瘤均有明显抗癌活性。CUDC-907对其他PI3K亚型有抑制作用抑制,如 PI3Kβ/γ/δ和 PI3KαE545K, IC50分别为 54/311/39/62 nM。而且, CUDC-907对HDAC亚型HDAC8//6/11(IC50:191/27/5.4 nM)也有抑制效果。此外,CUDC-907对其他类型 HDAC 酶活性也有微弱抑制。
激酶实验
The activities of classes I and II HDACs are measured using the Color-de-Lys assay system. The activity of PI3K is measured using the ADP-Glo luminescent kinase assay. Recombinant PI3K protein, a complex of N-terminal GST-tagged recombinant full-length human p110 and untagged recombinant full-length human p85, is coexpressed in a baculovirus-infected Sf9 cell expression system[1].
细胞实验
CUDC-907 is dissolved in DMSO and stored (-80°C), and then diluted with appropriate medium before use[1]. Human cancer cell lines are plated at densities of 5,000 to 10,000 per well in 96-well flat-bottomed plates with the recommended culture medium. The cells are then incubated with compounds (e.g.,CUDC-907) at various concentrations for 72 hours in culture medium supplemented with 0.5% (v/v) FBS. Growth inhibition is assessed by assay of cellular ATP content using the Perkin-Elmer ATPlite kit[1].
Cas No.
1339928-25-4
分子式
C23H24N8O4S
分子量
508.56
别名
CUDC 907;PI3K/HDAC Inhibitor;CUDC-907
储存和溶解度
Ethanol:<1 mgml
DMSO:94 mg/mL (184.8 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years